General Principles of General Principles of PathophysiologyPathophysiology

The Cellular EnvironmentThe Cellular EnvironmentFluids & ElectrolytesFluids & ElectrolytesAcid-base Balance & MaintenanceAcid-base Balance & Maintenance

TopicsTopics

Describe the distribution of water in the Describe the distribution of water in the bodybody

Discuss common physiologic electrolytesDiscuss common physiologic electrolytes Review mechanisms of transportReview mechanisms of transport

– osmosis, diffusion, etc Discuss hemostasis & blood typesDiscuss hemostasis & blood types Discuss concepts of acid-base maintenanceDiscuss concepts of acid-base maintenance

Distribution of WaterDistribution of Water

Total Body Weight/ Total Body WaterTotal Body Weight/ Total Body Water Intracellular - ICF (45%/75%)Intracellular - ICF (45%/75%) Extracellular - ECF (15%/25%)Extracellular - ECF (15%/25%)

– Intravascular (4.5%/7.5%)– Interstitial (10.5%/17.5%)

Intra-Intra-cellularcellular

45%45%31.5 kg31.5 kg

InterstitialInterstitial10.5 %10.5 %7.35 kg7.35 kg

Intra-Intra-vascularvascular

4.5%4.5%3.15 kg3.15 kg

Total Body WeightTotal Body Weight

Fluid DistributionFluid Distribution

Extracellular

Cel

l Mem

bran

e

Cap

illar

y M

embr

ane

Fluid DistributionFluid Distribution

Intra-Intra-cellularcellular

75%75%31.5 L31.5 L

InterstitialInterstitial17.5 %17.5 %7.35 L7.35 L

Intra-Intra-vascularvascular

7.5%7.5%3.15 L3.15 L

Total Body WaterTotal Body Water

Extracellular

Cel

l Mem

bran

e

Cap

illar

y M

embr

ane

Total Body WeightTotal Body Weight

45.0%

4.5%10.5%

0%5%10%15%20%25%30%35%40%45%50%

Intracellular Intravascular Interstitial

Total Body WaterTotal Body Water

75.0%

7.5%

17.5%

0%

10%20%

30%40%

50%

60%70%

80%

Intracellular Intravascular Interstitial

EdemaEdema

Fluid accumulation in the interstitial Fluid accumulation in the interstitial compartmentcompartment

Causes:Causes:– Lymphatic ‘leakage’– Excessive hydrostatic pressure– Inadequate osmotic pressure

Fluid IntakeFluid Intake

Water from beverages:1600 ml (64%)

Water from food:700 ml (28%)

Water from metabolism:200 ml (8%)

Fluid OutputFluid Output

Water from skin:550 ml (25%)

Water from feces:150 ml (5%)

Water from lungs: 300 ml (11%)

Water from urine: 1500 ml (59%)

Osmosis versus DiffusionOsmosis versus Diffusion

Osmosis is the net Osmosis is the net movement of water movement of water from an area of from an area of LOWLOW solute concentration to solute concentration to an area of an area of HIGHERHIGHER solute concentration solute concentration across a semi-across a semi-permeable membrane.permeable membrane.

diffusion of waterdiffusion of water– in terms of [water]

Diffusion is the net Diffusion is the net movement of solutes movement of solutes from an area of from an area of HIGHHIGH solute concentration to solute concentration to an area of an area of LOWERLOWER solute concentration.solute concentration.

Silly definition stuffSilly definition stuff

Osmolarity = Osmolarity = osmoles/L of solutionosmoles/L of solution

Osmolality = Osmolality = osmoles/kg of solutionosmoles/kg of solution

Where an osmole is 1 mole (6.02 x 10Where an osmole is 1 mole (6.02 x 102323 particles) particles)

The bottom line?The bottom line?Use them synonymously!Use them synonymously!

TonicityTonicity

IsotonicIsotonic HypertonicHypertonic HypotonicHypotonic

Isotonic SolutionsIsotonic Solutions

Same solute concentration as RBCSame solute concentration as RBC If injected into vein: no net movement of If injected into vein: no net movement of

fluidfluid Example: 0.9% sodium chloride solutionExample: 0.9% sodium chloride solution

– aka Normal Saline

Hypertonic SolutionsHypertonic Solutions

Higher solute concentration than RBCHigher solute concentration than RBC If injected into vein:If injected into vein:

– Fluid moves INTO veins

Hypotonic SolutionsHypotonic Solutions

Lower solute concentration than RBCLower solute concentration than RBC If injected into vein:If injected into vein:

– Fluid moves OUT of veins

Affects of Hypotonic Solution on Affects of Hypotonic Solution on CellCell

CellSwellingCell

SwollenCell

RupturedRupturedCellCell

The [solute] outside The [solute] outside the cell is lower than the cell is lower than inside. inside.

Water moves from low Water moves from low [solute] to high [solute] to high [solute].[solute].

The cell swells and The cell swells and eventually bursts!eventually bursts!

Affects of Hypertonic Solution on Affects of Hypertonic Solution on CellCell

Cell

The [solute] outside The [solute] outside the cell is higher than the cell is higher than inside. inside.

Water moves from low Water moves from low [solute] to high [solute] to high [solute].[solute].

The cell shrinks!The cell shrinks!Shrinking

CellShrunken

Cell

Infusion of Infusion of hypertonic hypertonic solution into veinssolution into veins

No fluid No fluid movementmovement

Fluid Fluid movement movement into veinsinto veins

Fluid Fluid movement movement out of veinsout of veins

Infusion of Infusion of isotonic solution isotonic solution into veinsinto veins

Infusion of Infusion of hypotonic solution hypotonic solution into veinsinto veins

Ion DistributionIon Distribution

0

50

100

150

50

100

150

mEq

/L NaNa++

KK++

ClCl--

POPO44--

ProteinProtein--

Cations Anions

Extracellular

Intracellular

Example of Role of ElectrolytesExample of Role of Electrolytes

Nervous SystemNervous System– Propagation of Action Potential

Cardiovascular SystemCardiovascular System– Cardiac conduction & contraction

Cardiac Conduction / ContractionCardiac Conduction / Contraction

Composition of BloodComposition of Blood

8% of total body weight8% of total body weight Plasma: 55%Plasma: 55%

– Water: 90%– Solutes: 10%

Formed elements: 45%Formed elements: 45%– Platelets– Erythrocytes

HematrocritHematrocrit

% of RBC in blood% of RBC in blood Normal: Normal:

– 37% - 47% (Female)– 40% - 54% (Male)

Blood ComponentsBlood Components

Plasma: liquid portion of bloodPlasma: liquid portion of blood Contains ProteinsContains Proteins

– Albumin (60%) contribute to osmotic pressure– Globulin (36%): lipid transport and antibodies– Fibrinogen (4%): blood clotting

Blood ComponentsBlood Components

Formed ElementsFormed Elements– Erythrocytes– Leukocytes– Thrombocytes

ErythrocytesErythrocytes

‘‘biconcave’ discbiconcave’ disc 7-8 mcm diameter7-8 mcm diameter Packed with hemoglobinPacked with hemoglobin 4.5 - 6 million RBC/mm4.5 - 6 million RBC/mm3 3 (males)(males) AnucleateAnucleate 120 day life span120 day life span 2 million replaced per second!2 million replaced per second!

LeukocytesLeukocytes

Most work done in tissuesMost work done in tissues 5,000 - 6,000/mm5,000 - 6,000/mm33

– Neutrophils (60-70%)– Basophils (Mast Cells) (<1%)– Eosinophils (2-4%)– Lymphocytes (20-25%)– Monocytes (Macrophages) (3-8%)

ThrombocytesThrombocytes

PlateletsPlatelets Cell fragmentsCell fragments 250,000 - 500,000/mm250,000 - 500,000/mm33

Form platelet plugsForm platelet plugs

HemostasisHemostasis

The stoppage of bleeding.The stoppage of bleeding. Three methodsThree methods

– Vascular constriction– Platelet plug formation– Coagulation

CoagulationCoagulation

Formation of blood clotsFormation of blood clots Prothrombin activatorProthrombin activator Prothrombin Prothrombin Thrombin Thrombin Fibrinogen Fibrinogen Fibrin Fibrin Clot retractionClot retraction

CoagulationCoagulation

ProthrombinProthrombinActivatorActivator

ProthrombinProthrombinThrombinThrombin

FibrinogenFibrinogen FibrinFibrin

ClotClot

FibrinolysisFibrinolysis

PlasminogenPlasminogen tissue plasminogen activator (tPA)tissue plasminogen activator (tPA) PlasminPlasmin

Blood TypesBlood Types

Agglutinogens (Blood Antigens)Agglutinogens (Blood Antigens) Agglutinins (Blood Antibodies)Agglutinins (Blood Antibodies) Agglutination (RBC clumping)Agglutination (RBC clumping) ABOABO Rh AntigensRh Antigens

Type A BloodType A Blood

Type B BloodType B Blood

Type AB BloodType AB Blood

Type O BloodType O Blood

Rh AntigensRh Antigens

Bottom line of Acid-BaseBottom line of Acid-Base

Regulation of [H+]Regulation of [H+]– normally about 1/3.5 million that of [Na+]– 0.00004 mEq/L (4 x 10-8 Eq/L)

Dependent uponDependent upon– Kidneys– Chemical Buffers

Precise regulation necessary for peak Precise regulation necessary for peak enzyme activityenzyme activity

pH Effects on Enzyme ActivitypH Effects on Enzyme Activity

pH

Enzy

me

Act

ivity

activity

Peak Activity

activity

Acid BaseAcid Base

Acids release HAcids release H++

– example: HCl -> H+ + Cl-

Bases absorb HBases absorb H++

– example: HCO3- + H+ -> H2CO3

pH is logarithmicpH is logarithmic

pH = log 1/[HpH = log 1/[H++]] = - log [H= - log [H++] ] = - log 0.00000004 Eq/L= - log 0.00000004 Eq/L pH = 7.4pH = 7.4

Think of pH as ‘power of [HThink of pH as ‘power of [H++]]

pH is LogarithmicpH is Logarithmic

pH is inversely pH is inversely related to [H+]related to [H+]

Small Small pH mean pH mean large large [H [H++]]

as as [H+] [H+] pH pH

as as [H+] [H+] pH pH

&

pH 7.4 = 0.00000004pH 7.4 = 0.00000004pH 7.1 = 0.00000008pH 7.1 = 0.00000008

(it doubled!) (it doubled!)

Buffers Resist pH ChangesBuffers Resist pH Changes

Weak acid & conjugate base pairWeak acid & conjugate base pair HH22COCO33 HCO HCO33

-- + H + H++

Conjugate Acid Conjugate Acid conjugate base + acid conjugate base + acid

Henderson-Hasselbalch EquationHenderson-Hasselbalch Equation

pH = pKpH = pKaa + log [base]/[acid] + log [base]/[acid]– Ex:

• = 6.1 + log 20/1• = 6.1 + 1.3• = 7.4

Key ratio is base: acidKey ratio is base: acid– HCO3

- : CO2 (standing in for H2CO3)

pH ScalepH Scale

0 : Hydrochloric Acid0 : Hydrochloric Acid 1: Gastric Acid1: Gastric Acid 2: Lemon Juice2: Lemon Juice 3: Vinegar, Beer3: Vinegar, Beer 4: Tomatoes4: Tomatoes 5: Black Coffee5: Black Coffee 6: Urine6: Urine 6.5: Saliva6.5: Saliva

7: Blood7: Blood 8: Sea Water8: Sea Water 9: Baking Soda9: Baking Soda 10: Great Salt Lake10: Great Salt Lake 11: Ammonia11: Ammonia 12: Bicarbonate12: Bicarbonate 13: Oven Cleaner13: Oven Cleaner 14: NaOH14: NaOH

Acid Base CompensationAcid Base Compensation

Buffer SystemBuffer System Respiratory SystemRespiratory System Renal SystemRenal System

Buffer SystemBuffer System

ImmediateImmediate COCO22 + H + H220 0 H H22COCO33 H H++ + HCO + HCO33

--

Equilibrium: 20 HCOEquilibrium: 20 HCO33-- to 1 CO to 1 CO22 (H (H22COCO33))

Excessive COExcessive CO22 acidosis acidosis Excessive HCOExcessive HCO33

-- alkalosis alkalosis

Simplified:CO2 H+

Question...Question...

Is the average pH of the blood lower in:Is the average pH of the blood lower in:

a) arteriesa) arteriesb) veinsb) veins

Veins! Veins! Why?Why?

Because veins pick up the Because veins pick up the byproducts of cellular metabolism, byproducts of cellular metabolism,

including…including…COCO22!!

Respiratory SystemRespiratory System

MinutesMinutes COCO22 H H++

Respiration Respiration : CO: CO22 : H: H++ Respiration Respiration : CO: CO22 : H: H++

Renal SystemRenal System

Hours to daysHours to days Recovery of BicarbonateRecovery of Bicarbonate Excretion of HExcretion of H++

Excretion of ammoniumExcretion of ammonium

DisordersDisorders

Respiratory AcidosisRespiratory Acidosis Respiratory AlkalosisRespiratory Alkalosis Metabolic AcidosisMetabolic Acidosis Metabolic AlkalosisMetabolic Alkalosis

Respiratory AcidosisRespiratory Acidosis

COCO22 + H + H220 0 H H22COCO33 H H++ + HCO + HCO33

•Simplified:

CO2 H+

Respiratory AlkalosisRespiratory Alkalosis

COCO22 + H + H220 0 H H22COCO33 H H++ + HCO + HCO33

• Simplified:

CO2 H+

Metabolic AcidosisMetabolic Acidosis

HH++ + HCO + HCO33 H H22COCO33 H H220 + 0 + CO CO22

•Simplified:

•Producing too much H+

Metabolic AlkalosisMetabolic Alkalosis

HH++ + HCO + HCO33 H H22COCO33 H H220 + 0 + CO CO22

•Simplified:

•Too much HCO3

Normal ValuesNormal Values

pH: 7.35 - 7.45pH: 7.35 - 7.45 PCOPCO22: 35 - 45: 35 - 45

Abnormal ValuesAbnormal Values

pH PCO2

Respiratory Acidosis

Respiratory Alkalosis

Metabolic Acidosis Normal if compensating

Metabolic Alkalosis Normal if compensating

All Roads Lead to Rome!All Roads Lead to Rome!

Respiratory OpposesRespiratory Opposes

Metabolic EqualsMetabolic Equals(or doesn’t oppose)(or doesn’t oppose)

Example:Example:

pH = 7.25pH = 7.25 PCOPCO22 = 60 = 60

RespiratoryRespiratoryAcidosis!Acidosis!

Example:Example:

pH = 7.50pH = 7.50 PCOPCO22 = 35 = 35

MetabolicMetabolicAlkalosis!Alkalosis!

Example:Example:

pH = 7.60pH = 7.60 PCOPCO22 = 20 = 20

RespiratoryRespiratoryAlkalosis!Alkalosis!

Example:Example:

pH = 7.28pH = 7.28 PCOPCO22 = 38 = 38

MetabolicMetabolicAcidosis!Acidosis!

ResourcesResources

A Continuing Education article on Acid-A Continuing Education article on Acid-Base disturbances is available on our web Base disturbances is available on our web site at:site at:

http://www.templejc.edu/ems/resource.htmhttp://www.templejc.edu/ems/resource.htm A great online tutorial at:A great online tutorial at: http://www.tmc.tulane.edu/departments/http://www.tmc.tulane.edu/departments/

anesthesiology/acid/acid.htmlanesthesiology/acid/acid.html